US2021128526A1PendingUtilityA1

Eye drops to treat chemically induced corneal damage

37
Individually held — no corporate assignee on recordPriority: Nov 5, 2019Filed: Nov 5, 2020Published: May 6, 2021
Est. expiryNov 5, 2039(~13.3 yrs left)· nominal 20-yr term from priority
Inventors:Rajiv R. Mohan
A61K 31/401A61P 29/00A61K 31/167A61K 45/06A61K 31/375A61K 31/407A61K 9/0048
37
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Claims

Abstract

Provided herein are compositions suitable for treating chemically induced eye damage comprising (a) a nonsteroidal anti-inflammatory drug (NSAID), (b) a histone deacetylase (HDAC) inhibitor and (c) an angiotensin converting enzyme (ACE) inhibitor and, optionally, (d) a water-soluble vitamin. Methods of using provided compositions to treat ocular toxicity and corneal damage following exposure to chemical agents (e.g., mustard gas) are also provided.

Claims

exact text as granted — not AI-modified
1 . An composition comprising:
 (a) a nonsteroidal anti-inflammatory drug (NSAID);   (b) a histone deacetylase (HDAC) inhibitor; and   (c) an angiotensin converting enzyme (ACE) inhibitor.   
     
     
         2 . The composition of  claim 1  comprising from about 0.1% to about 5% of the NSAID. 
     
     
         3 . The composition of  claim 2  comprising about 0.5% of the NSAID. 
     
     
         4 . The composition of  claim 1  comprising from about 1 μM to about 50 μM of the HDAC inhibitor. 
     
     
         5 . The composition of  claim 4  comprising about 25 μM of the HDAC inhibitor. 
     
     
         6 . The composition of  claim 1  comprising from about 1 μM to about 50 μM of the ACE inhibitor. 
     
     
         7 . The composition of  claim 6  comprising about 25 μM of the ACE inhibitor. 
     
     
         8 . The composition of  claim 1  wherein the NSAID is selected from the group consisting of diclofenac sodium, flubiprofen sodium, ketorolac, bromfenac, nepafenac, and any combination thereof. 
     
     
         9 . The composition of  claim 1  wherein the NSAID comprises ketorolac. 
     
     
         10 . The composition of  claim 1  wherein the HDAC inhibitor is selected from the group consisting of vorinostat (suberoylanilide hydroxamic acid, SAHA), trichostatin A (TSA), panobinostat (LBH589), belinostat (PXD101), romidepsin (FK228), entinostat (MS-275), mocetinostat (MGCD0103), valproic acid (VPA), sodium butyrate (NaB), and phenylbutyrate (PBA). 
     
     
         11 . The composition of  claim 1  wherein the HDAC inhibitor inhibits Class I and Class II HDACs. 
     
     
         12 . The composition of  claim 1  wherein the HDAC inhibitor comprises suberoylanilide hydroxamic acid (SAHA). 
     
     
         13 . The composition of  claim 1  wherein the ACE inhibitor is selected from the group consisting of enalapril, benazepril, captopril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril and any combination thereof. 
     
     
         14 . The composition of  claim 1  wherein ACE inhibitor comprises enalapril. 
     
     
         15 . The composition of  claim 1  further comprising a water-soluble vitamin. 
     
     
         16 . The composition of  claim 15  comprising from about 1% to about 20%, of the water-soluble vitamin. 
     
     
         17 . The composition of  claim 15  wherein the water-soluble vitamin comprises Vitamin C (ascorbic acid). 
     
     
         18 . The composition of  claim 1  wherein the composition inhibits a cyclooxygenase-2 (COX2), a matrix metallopeptidase (MMP), an inducible nitric oxide synthase (iNOS), myofibroblast formation, neovascularization or a combination of any thereof. 
     
     
         19 . The composition of  claim 1  comprising about 0.5 wt. % or vol. % of ketorolac, about 25 μM of suberoylanilide hydroxamic acid (SAHA), about 25 μM of enalapril, and about 10 wt. % of ascorbic acid. 
     
     
         20 . The composition of  claim 1  further comprising a pharmaceutically appropriate carrier. 
     
     
         21 . A method of treating corneal damage and/or ocular toxicity in a subject in need thereof, the method comprising administering to an eye of the subject the composition of  claim 1 .

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